Migraine + Anti-emetic Flashcards
What are the four components of migraine syndrome?
PRODROME
= vague changes in mood, appetite
AURA
= neurological disturbances
HEADACHE
RESOLUTION
Characterize a migraine headache
Throbbing
Usually one-sided
N/V, gastric stasis, photophobia, and/or phonophobia
What is the neurovascular theory?
Abnormal neural activation
Leads to…
Vasodilation, local inflammation
= MIGRAINE!
What is cortical spreading depression (CSD)?
Wave of strong depolarization that spreads slowly over the cortical surface
Followed by prolonged depression
What happens following CSD cording to neurovascular theory for migraine?
CSD in cortex leads to release of K+, H+, NO and PGs into interstitial fluid.
These mediators cross meningeal blood vessel and stimulate nerve endings
Substance P and CGRP are released and can lead to release of inflammatory mediators from mast cells, and plasma extravasation
What class of drugs are very effective against migraine,
Decreasing release of
Substance P
CGRP
Vasoconstriction
5-HT agonists
1B and 1D
What are general therapies for acute migraine?
NSAIDs (+/- caffeine)
Antiemetics
+Metoclopramide
Opioid analgesics = last resort!
What are specific therapies for acute migraine?
5-HT (1B/1D) agonists
= “triptans”
= sumatriptan
Ergo Alkaloids
= Ergotamine, Dihydroergotamine
What are adverse effects of “triptans”?
Paresthesias, flushing, fatigue, dizziness, nausea
Heavy/tightness in chest
Peripheral vasoconstriction + vasospasm
What are CIs for “triptans”?
CAD
Cerebrovascular disease
PVD
Uncontrolled HTN
What are DDIs associated with “triptans”?
Metabolized by MAO
- MAO inhibitors
Used in caution with patients taking SSRIs or SNRIs to avoid serotonin syndrome
What AEs are associated with ergot alkaloids?
N/V
Can cause fetal distress and uterine contractions
Fibrotic thickening of cardiac valves
Peripheral vasoconstriction ‼️‼️
What are symptoms of ergot poisoning?
Vascular occlusion
limb ischemia
Gangrene
What are CIs associated with ergot alkaloids?
CAD
PVD
Uncontrolled HTN
Pregnancy
What are prophylactic agents for migraine?
1st line =
+beta antagonists (propranolol, timolol, metoprolol)
+antiepileptic drugs (valproic acid, divalproex, topiramate)
+antidepressants (amitriptyline, venlafaxine)
ACEIs, ARBs (lisinopril, candesartan)
CCBs (verapamil)
Muscle relaxants (Botox)
What are alternative therapies for prevention of migraine?
Butterbur extract
**best evidence
CoQ10 Feverfew Riboflavin Mg Melatonin
What receptors when stimulated involve N/V?
5HT3
D2
mAChR
H1
NK1
What inputs contribute to the vomiting response?
Chemoreceptor trigger zone (CTZ) = 5HT3, D2, opioid, NK1(?)
Vestibular apparatus =mAChR, H1
Higher centers = odor, tastes, fear
Stomach Small intestine = 5HT3
Pharynx = gagging
What are causes of 5HT3 mediated emetic effects?
CINV
Radiation
Acute gastroenteritis
Aspirin, ferrous sulfate, other drugs
Surgery
(Serotonin released by intestinal irritants)
What are examples of 5HT3 antagonists?
“Setrons”
What are AEs associated with 5HT3 antagonists?
Mild headache/dizziness
Constipation
All (except palonosetron) can inc. QT interval
What are indications for 5HT3 antagonists?
Acute CINV
(Enhanced with NK1 antagonist and corticosteroid)
RINV
PONV
Acute gastroenteritis induced NV
What are examples of DA agonists?
How do they contribute to emetic effects?
Can induce NV by stimulating D2 receptors in CTZ
Ropinirole
Pramipexole
Rotigotine
What are examples of D2 ANTAgonists ???
Proclorperazine
Chlorpromazine
Metoclopramide
What can D2 antagonists for antiemetic effects lead to?
Can cause EPS
(Motor symptoms from dopamine blockade)
Diphenhydramine can be administered to prevent or attenuate acute dystonia when agents given parenterally at high doses
What is the black box warning associated with a D2 antagonist antiemetic agent?
Metoclopramide
Chronic use => tardive dyskinesia
What are indications for phenothiazines and metoclopramide?
Phenothiazines
=general purpose (not CINV)
Metoclopramide \+PONV \+migraine-induced NV \+GI motility disorders \+CINV
What mAChR antagonist is used for antiemetic effects?
Scopolamine
What AEs and CIs are associated with scopolamine?
AEs
- Xerostomia
- constipation
- urinary retention
- drowsiness
- visual disturbances
CIs/cautions:
- glaucoma
- GI, urinary tract obstruction
- BPH
What H1 antihistamines are used as antiemetic agents?
Diphenhydramine
Dimenhydrinate
Meclizine
What are examples of NK1 receptor antagonists used as antiemetic agents?
“Pitants”
Aprepitant
Netupitant
Rolapitant
What are indications for NK1 receptor antagonists?
CINV
PONV = aprepitant
What corticosteroid is used as an antiemetic?
What are the indications?
Dexamethasone
CINV
PONV
What cannabinoids are used for antiemetic function?
What are the indications and AEs?
Dronabinol
Nabilone
indication: CINV
AEs:
- euphoria/dysphoria
- vertigo
- paranoia
- inc. appetite
When are benzodiazepines used as antiemetics?
Weak antiemetic effects used as adjunct to prevent CINV and PONV
